Laparoscopic Cholecystectomy Update

SUMMARY RECOMMENDATIONSPROSPECT laparoscopic cholecystectomy update 2006 SubgroupFor each review, a Subgroup of the PROSPECT Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. The Subgroup may sometimes include a non-Working Group member, to provide additional expertise in the procedure being reviewed.

For the laparoscopic cholecystectomy update 2006 review, the Subgroup members were:

PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.

Summary RecommendationsPre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following laparoscopic cholecystectomy. Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision, ‘intra-operative’ refers to interventions applied after incision and before wound closure, ‘postoperative’ refers to interventions applied at or after wound closure. The following peri-operative interventions for laparoscopic cholecystectomy have been reviewed:

Transferable evidence of analgesic efficacy from comparable procedures or evidence of other outcomes, such as adverse effects, has been included to support the procedure-specific evidence where this is insufficient.

In certain circumstances, recommendations for a type of treatment cannot be made due to limited or conflicting evidence. Areas which have been identified as requiring further investigation in the future are as follows:

PROSPECT Recommendations

Pre-operative systemic clonidine is not recommended (Grade D) because procedure-specific evidence for analgesic efficacy is limited and because of potential adverse-effects, which may delay early ambulation (LoE 4)

Clinical Practice

The risk/benefit ratio for clonidine is unclear. Recognised side-effects include hypotension, sedation, dizziness and bradycardia

Laparoscopic Cholecystectomy-specific evidence

Pre-operative clonidine significantly reduced the incidence of nausea compared with placebo (p<0.05), but there was no significant difference between groups for the incidence of vomiting Sung et al 2000

Pre-operative clonidine did not reduce VAS pain scores compared with placebo at any time point (i.e. 0–120 minutes after surgery) Sung et al 2000

PROSPECT Recommendations

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004

Clinical Practice

Transferable Evidence from Other Procedures

A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritis, urinary retention or respiratory depression Marret et al 2005

A large randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002

Conventional NSAIDs and COX-2 selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003

Short-term use of conventional NSAIDs or COX-2 selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004

Laparoscopic Cholecystectomy-specific evidence

Eight studies out of ten showed a significant benefit of conventional NSAIDs over placebo or no treatment for reducing VAS pain scores; in most cases the benefit was limited to the very early postoperative period Munro et al 1998Click here for more information

One study measured parameters of pulmonary function and found that the values of FEV1 and FEF25–75 were significantly higher at 4 h after surgery in the ketorolac group compared with the placebo group (p<0.05) Liu et al 1993

One study out of one showed that tenoxicam (20 mg) + ondansetron (4 mg), administered in 20 ml saline before induction of anaesthesia, significantly reduced the time to first flatus compared with ondansetron alone (p<0.05) Elhakim et al 1995

Pre-operative ketoprofen significantly reduced VAS pain scores compared with postoperative ketoprofen during the first 12 h following surgery (p<0.05), with the effect being most evident during the first 3 h (p=0.001), although there was no significant difference between the two groups at 24 h Boccara et al 2005

One study showed that pre-operative ketoprofen significantly increased the time to first analgesic demand compared with pre-operative propacetamol, but there was no significant difference between the agents given postoperatively&nbsp Boccara et al 2005

One study showed that pre-operative administration of IV tenoxicam + IM dextromethorphan was associated with significantly lower VAS pain scores than IV saline + IM dextromethorphan at 1 and 2 h at rest and at 1, 2 and 4 h on coughing (p<0.05 in each case), but not at other time points (data was collected at 1, 2, 4, 12, 24 and 48 h) Yeh et al 2004

The time to first analgesic request was significantly longer in the IV tenoxicam + IM dextromethorphan group compared with IV saline + IM dextromethorphan (p<0.001) Yeh et al 2004

Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with significantly lower VAS pain scores at 0, 0.5, 1, 2, 3 and 4 h after arrival in PACU, then at discharge and at 10 h (p<0.05 in each case) but not at 24 or 48 h; and also reduced VRS pain scores at all time points, except at 24 h (p<0.05) Michaloliakou et al 1996

Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with a significantly greater proportion of patients without pain on arrival in PACU and with only mild pain at discharge (p<0.001 in each case)&nbsp Michaloliakou et al 1996

Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with a significantly longer time to first analgesic request (p<0.001) Michaloliakou et al 1996

Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with a significantly shorter time to discharge from PACU (p<0.05), although the time to the first bowel movement was similar in both groups Michaloliakou et al 1996

Compared with placebo, a regimen of conventional NSAID plus strong opioid, followed by LA infiltration, was associated with significantly reduced nausea scores in PACU (p<0.05), but there was no significant difference at any other time Michaloliakou et al 1996

Only two studies out of seven that recorded the incidence of nausea and/or vomiting showed that conventional NSAIDs significantly reduced the incidence of nausea and/or vomiting compared with placebo or no treatment Elhakim et al 1995Click here for more information

There was no significant difference in the incidence of nausea or vomiting between pre-operative and postoperative administration of ketoprofen Boccara et al 2005

There were no significant differences between ketoprofen and propacetamol for the incidence of nausea or vomiting, administered pre- or post-operatively Boccara et al 2005

One study out of one found no significant differences for the duration of hospital stay between IM ketorolac, administered intra-operatively pre- and post-procedure, and placebo Lane et al 1996

One study out of one found no significant difference for the time to hospital discharge between IM diclofenac, administered after induction of anaesthesia (n=26), and placebo (n=23) Wilson et al 1994

One study out of one found that VAS pain scores in the IV tenoxicam + IM chlorpheniramine group were significantly higher than those in the IV saline + IM dextromethorphan + IM chlorpheniramine group at 1 h at rest and at 2 and 4 h on coughing (p<0.05 in each case), but not at other time points (VAS pain scores were recorded at 1, 2, 4, 12, 24 and 48 h) Yeh et al 2004

One study out of one found that the time to first analgesic request, pethidine use and the incidence of pethidine-related side-effects were not significantly different between the IV tenoxicam + IM chlorpheniramine and the IM dextromethorphan groups + IM chlorpheniramine Yeh et al 2004

One study out of one found that the incidence of pethidine-related side-effects, such as nausea and vomiting, was similar in both the IV tenoxicam + IM dextromethorphan and the IV saline + IM dextromethorphan groups Yeh et al 2004

There was no significant difference between the four doses of dexamethasone (2, 4, 8, 16 mg) for VAS pain scores at rest or with activity (each group received ondansetron 4 mg) Elhakim et al 2002

There was no significant difference between the four doses of dexamethasone (2, 4, 8, 16 mg) for opioid use at 12 and 24 h after surgery (each group received ondansetron 4 mg)&nbsp Elhakim et al 2002

There were no significant differences between the four doses of dexamethasone (2, 4, 8, 16 mg) for the incidence of PONV, antiemetic use and duration of hospital stay (each group received ondansetron 4 mg) Elhakim et al 2002

Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004

Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a

Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003

One study showed that pre-operative celecoxib and placebo were similar for abdominal and trocar entry site VAS pain scores at rest and during coughing at 0–6 h, and 12 and 24 h; both groups were similar for shoulder pain VRS Cheng et al 2004

There was no significant difference between celecoxib and placebo for the cumulative morphine consumption over the first 24 h following surgery Cheng et al 2004

One study showed that patients in both celecoxib and placebo groups took a similar length of time for analgesic request and had a similar severity of nausea and vomiting Cheng et al 2004

Parecoxib/valdecoxib was associated with reduced incidence of vomiting at 24 h post-discharge (p<0.05) compared with placebo, but overall incidence of PONV throughout the study period was not reduced Gan et al 2004Click here for more information

There was no significant difference for bleeding tendency between celecoxib and placebo Cheng et al 2004

PROSPECT Recommendations

IV LA infusion is not recommended (Grade D) because procedure-specific evidence for analgesic efficacy is limited

Clinical Practice

IV LA infusion is not commonly used in routine clinical practice

Transferable Evidence from Other Procedures

[None cited]

Laparoscopic Cholecystectomy-specific evidence

IV lidocaine infusion significantly reduced VAS pain scores on coughing compared with placebo for 12 h following surgery (p<0.05), but not at 24 or 48 h, and only for 2 h at rest&nbsp Wu CT et al 2005

Compared with placebo, IV lidocaine infusion + IM dextromethorphan significantly reduced VAS pain scores at rest for the first 12 h postoperatively (p<0.05), but not at 24 and 48 h, and on coughing for the first 24 h (p<0.05), but not at 48 h&nbsp Wu CT et al 2005

IV lidocaine infusion + IM dextromethorphan significantly reduced VAS pain scores at rest at 1 and 4 h (p<0.05), and on coughing for the first 24 h (p<0.05), compared with either agent alone, but not at other time points (VAS measured at 1, 4, 12, 24 and 48 h)&nbsp Wu CT et al 2005

Total pethidine consumption was significantly lower in the IV lidocaine infusion group compared with the placebo group (p<0.001), as was the proportion of patients requiring pethidine (p<0.01) Wu CT et al 2005

PROSPECT Recommendations

Pre-operative dextromethorphan is not recommended (Grade D) because procedure-specific evidence for analgesic efficacy is limited and transferable evidence is inconclusive (LoE 4)

Pre-operative single dose ketamine is not recommended (Grade D) because procedure-specific evidence is limited, despite analgesic efficacy in other procedures (LoE 1)

Magnesium is not recommended (Grade B), due to lack of efficacy (LoE 1)

Clinical Practice

NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its CNS adverse effects, toxicity and for causing dysphoria

Transferable Evidence from Other Procedures

Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine Bell et al 2006

A study in gynaecological surgery that compared magnesium with placebo (placebo group received saline, magnesium groups received 40 mg/kg at induction, followed by either, saline, or magnesium infusion 10 mg/kg or 20 mg/kg), showed that morphine consumption was higher in the placebo group compared with the magnesium groups (total n=80) Seyhan et al 2006

A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases Duedahl et al 2006

In abdominal hysterectomy, NMDA-receptor antagonists provided no significant benefit over placebo for reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the specific type of agent and timing of administration Burstal et al 2001Click here for more information

One study out of one found that VAS pain scores in the IM dextromethorphan + IM chlorpheniramine maleate + IV saline group were significantly lower than those in the IV tenoxicam + IM chlorpheniramine maleate group at 1 h at rest and at 2 and 4 h on coughing (p<0.05, in each case), but not at other time points (VAS pain scores were recorded at 1, 2, 4, 12, 24 and 48 h) Yeh et al 2004

One study showed that pre-operative administration of IV tenoxicam + IM dextromethorphan + IM chlorpheniramine maleate was associated with significantly lower VAS pain scores than IV saline + IM chlorpheniramine maleate at 1 and 2 h at rest and at 1, 2 and 4 h on coughing (p<0.05 in each case), but not at other time points recorded (i.e. at 1, 2, 4, 12, 24 or 48 h) Yeh et al 2004

Compared with placebo, IM dextromethorphan + IV lidocaine significantly reduced VAS pain scores at rest for the first 12 h postoperatively (p<0.05), but not at 24 or 48 h, and on coughing for the first 24 h (p<0.05), but not at 48 h (each group received IM chlorpheniramine maleate) Wu CT et al 2005

Total pethidine consumption (1 mg/kg IM pethidine was given if requested) was significantly lower in the pre-operative IM dextromethorphan group compared with the intra-operative IM dextromethorphan group (p<0.0001) Wu et al 1999

IV ketamine infusion significantly reduced pain compared with placebo: VAS pain scores at rest at 2–4 h (p<0.05 in each case), but not at 0, 1, 8 or 20 h; VRS pain scores at 2 and 3 h (p<0.05 in each case), but not at other time points Ayoglu et al 2005

IV ketamine infusion significantly reduced VAS pain scores at rest compared with magnesium at 4 and 20 h (p<0.05 in both cases), but not at 0–4 h or at 8 h; ketamine also significantly reduced VRS pain scores compared with magnesium at 4 h ( p<0.05), but not at other time points Ayoglu et al 2005

One study out of one found that the time to first analgesic request, pethidine use and the incidence of pethidine-related side-effects were not significantly different between the IV tenoxicam + IM chlorpheniramine maleate and the IM dextromethorphan + IM chlorpheniramine maleate + IV saline groups Yeh et al 2004

One study out of one found that the incidence of pethidine-related side-effects, such as nausea and vomiting, was similar in both the IV tenoxicam + IM dextromethorphan + IM chlorpheniramine maleate and the IM chlorpheniramine maleate + IV saline groups Yeh et al 2004

In two out of three studies, the incidence of adverse effects, such as nausea and vomiting, was similar in the IM dextromethorphan + IM chlorpheniramine maleate + IV saline and the IM chlorpheniramine maleate + IV saline groups Wu et al 1999Click here for more information

There were no significant differences between pre-operative and intra-operative IM dextromethorphan treatment groups for the incidence of nausea or vomiting Wu et al 1999

IV magnesium infusion did not significantly reduce VAS or VRS pain scores compared with placebo at any time during 0–20 h Ayoglu et al 2005

Pre-operative and postoperative (R)-ketamine (bolus dose) were similar to placebo for pethidine use in the first 4 h, and for use of paracetamol + codeine at 24 h and 7 days postoperatively (postoperative analgesia: bolus doses of 0.1 mg/kg pethidine, 5-minute lockout, for 4 h, and after discharge, 500 mg paracetamol + 30 mg codeine) Mathisen et al 1999

Immediately after surgery (i.e. at 0 h), sufentanil significantly reduced VRS pain scores compared with remifentanil (p=0.04), but there were no significant differences at all other time points (1–120 h)&nbsp Damen et al 2004

Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated with significantly lower VAS pain scores at 0, 0.5, 1, 2, 3 and 4 h after arrival in PACU, then at discharge and at 10 h (p<0.05 in each case) but not at 24 or 48 h; and also reduced VRS pain scores at all time points, except at 24 h (p<0.05) Michaloliakou et al 1996

Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated with a significantly greater proportion of patients without pain on arrival in PACU and with only mild pain at discharge (p<0.001 in each case) Michaloliakou et al 1996

Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated with a significantly longer time to first analgesic request (p<0.001) Michaloliakou et al 1996

Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated significantly shorter time to discharge from PACU (p<0.05), although the time to the first bowel movement was similar in both groups Michaloliakou et al 1996

Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA infiltration, was associated significantly reduced nausea scores in PACU (p<0.05), but there was no significant difference at any other time Michaloliakou et al 1996

There were no significant differences between pre-operative IV morphine and placebo for VAS pain scores at rest or on coughing at any time point (i.e. 0–180 minutes) Munoz et al 2002

There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for VAS pain scores at rest or on coughing at any time point Munoz et al 2002

Pre-operative IV morphine and placebo groups took a similar length of time to first analgesic request Munoz et al 2002

There was no significant difference between pre-operative IV morphine and placebo groups for the incidence of postoperative emesis, although this was higher in the morphine group Munoz et al 2002

There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for opioid use (2–3 mg IV morphine was given when VAS pain 50 or greater), the incidence of emesis, or the length of time for first analgesia request&nbsp Munoz et al 2002

There were no significant differences between the remifentanil and sufentanil treatment groups for the use of supplementary analgesia, this being low in both groups (10 mg morphine and 100 mg diclofenac were given on demand, up to 60 mg morphine and 200 mg diclofenac/day) Damen et al 2004

Remifentanil and sufentanil were similar for the incidence of vomiting and VRS nausea scores at all time points and they were also similar for the time to discharge Damen et al 2004

PROSPECT Recommendations

Pre-operative tramadol is not recommended (Grade B) for analgesia because of side-effects during recovery (transferable evidence, LoE 1)

Clinical Practice

Tramadol is a centrally acting analgesic with µ-opioid agonist (M1-metabolite) and aminergic mechanisms of action. For prescription purposes, it is considered a weak opioid or a non-narcotic in most countries

Tramadol is useful in the treatment of postoperative pain of moderate intensity (intravenous and oral administration), providing effective analgesia in the in-patient and ambulatory setting

The effects of weak opioids on gastrointestinal (transit, secretion) and sphincter function, are of a lesser magnitude than those of strong opioids

At recommended doses, tramadol has no clinically relevant effects on cardiovascular or respiratory parameters, thus the risk of respiratory depression is negligible

Tramadol is beneficial when conventional NSAIDs are contraindicated

The oral solution (drops) of tramadol is useful as rescue medication when paracetamol/conventional NSAIDs/COX-2-selective inhibitor analgesic regimens are used

Opioid adverse effects, especially nausea and dizziness, limit the usefulness of tramadol, but many of the effects are less than for strong opioids

When ondansetron is used for the treatment/prophylaxis of tramadol-induced nausea and vomiting, a decrease in analgesic efficacy has been reported

Transferable Evidence from Other Procedures

Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients Moore et al 1997

A systematic review found that the combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to tramadol 100 mg but with a lower incidence of adverse effects Collins et al 2000

A systematic review found that the combination of codeine with paracetamol provided additional pain relief compared with paracetamol alone Moore et al 2000

Laparoscopic Cholecystectomy-specific evidence

Oral tramadol significantly reduced opioid use compared with placebo over the first 24 h following surgery (p<0.05; 2 µg/kg IV fentanyl was given on request)&nbsp Pandey et al 2004

The incidence of nausea/retching/vomiting was similar in both oral tramadol and placebo groups Pandey et al 2004

The incidence of nausea/retching/vomiting or sedation was similar in both oral tramadol and oral gabapentin groups Pandey et al 2004

The incidence of nausea and vomiting and of cardiovascular adverse events was similar in both the pre-operative IV tramadol + postoperative IV tramadol PCA group and pre-operative IV morphine + postoperative IV morphine PCA group Naguib et al 1998

Pre- and postoperative IV tramadol were associated with significantly higher VAS pain scores at 30, 45 and 90 minutes following surgery, but not at any other time during 2–24 h, compared with pre- and postoperative IV morphine (p<0.05); pain scores recorded by an observer were similar between groups Naguib et al 1998

PCA drug consumption in the early postoperative period was significantly greater in the pre-operative IV tramadol + postoperative IV tramadol group compared with the pre-operative IV morphine + postoperative IV morphine PCA group Naguib et al 1998Click here for more information

There were no significant differences between pre-operative IV tramadol + postoperative IV tramadol PCA and pre-operative IV morphine and postoperative IV morphine PCA groups for the time taken to the first analgesic demand or for the proportion of patients not requesting PCA analgesia Naguib et al 1998

The incidence of sedation and respiratory depression was significantly higher in the oral tramadol group compared with the placebo group (p<0.05 in both cases)&nbsp Pandey et al 2004

The incidence of respiratory depression was significantly higher in the oral tramadol group compared with the oral gabapentin group (p<0.05) Pandey et al 2004

A meta-analysis of randomised controlled trials showed that paracetamol combined with PCA morphine induced a significant morphine-sparing effect but did not change the incidence of morphine-related adverse effects in the postoperative period Remy 2005

There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone Altman 2004

Laparoscopic Cholecystectomy-specific evidence

The number of patients requiring supplemental nalbuphine, the total dose consumed and the time to first analgesic demand were similar in both pre-operative and postoperative propacetamol groups Boccara et al 2005

There were no significant differences between pre-operative ketoprofen and pre-operative propacetamol groups for the incidence of nausea or vomiting Boccara et al 2005

The incidence of nausea or vomiting was similar in both pre-operative and postoperative propacetamol groups Boccara et al 2005

Pre-operative propacetamol was associated with a significantly shorter time to first analgesic demand compared with pre-operative ketoprofen (p<0.05) (p-value given for the overall 4-group comparison) Boccara et al 2005

Pre-operative propacetamol was associated with significantly greater opioid use compared with pre-operative ketoprofen, but there was no significant difference between these agents given postoperatively Boccara et al 2005Click here for more information

Postoperative administration of propacetamol significantly reduced VAS pain scores between 2 and 5 h postoperatively compared with pre-operative administration (p<0.05); the number of patients with severe pain (VAS 50 mm or greater) was significantly lower in the postoperative administration group compared with the pre-operative administration group (p<0.05) Boccara et al 2005

A qualitative systematic review of incisional local anaesthesia for postoperative pain relief after abdominal operations showed that except for herniotomy, there was a lack of evidence for a beneficial effect of incisional local anaesthesia on postoperative pain Møiniche et al 1998

Two quantitative systematic reviews of studies performed in a variety of procedures found no significant analgesic benefit of pre-incisional local anaesthetic wound infiltration compared with similar post-incisional wound infiltration Møiniche et al 2002

Laparoscopic Cholecystectomy-specific evidence

Nine out of 11 studies showed a significant benefit of LA wound infiltration over placebo or no treatment for reducing VAS pain scores, see Table 2a for details Click here for more information

In one study out of one, the proportion of patients with most severe pain located to the right lower abdominal wall on day 2 was significantly lower in the pre-incisional LA (bupivacaine) infiltration group compared with the placebo group (p=0.012) Ure et al 1993

In one study out of one, the proportion of patients with no pain after 5 h was significantly higher in the pre-incisional LA infiltration group compared with the placebo group (p=0.03) Ure et al 1993

Two studies out of two found that LA wound infiltration significantly increased the time to first analgesic demand compared with placebo (p<0.05 in both cases) Papaziogas et al 2001

Six studies out of 11 reported that LA wound infiltration reduced analgesic consumption compared with placebo or no treatment, see Table 2a for details; each of those studies also showed significantly reduced VAS pain scores with LA wound infiltration Click here for more information

In one study out of one, the rate of same-day discharge was significantly higher in the LA wound infiltration (bupivacaine + epinephrine) group compared with the no infiltration group (p<0.05)&nbsp Dath and Park 1999

There were no significant differences for VAS pain scores between pre-incisional LA and postoperative LA administration groups at any of the time points recorded (i.e. 1, 3, 5, 7 and 12 h in the Sarac et al 1996

Pre-incisional ropivacaine significantly reduced NSAID (diclofenac) consumption (patients with VAS scores of 3 or greater were given 50–100 mg diclofenac, rectally) compared with pre-incisional levobupivacaine (p<0.001), but parenteral opioid use was similar between groups (patients with persistent pain were given parenteral opioids) Papagiannopoulou et al 2003

IV ketamine + ropivacaine infiltration significantly decreased VAS pain scores compared with placebo at 6 and 12 h (p<0.05 in each case) as well as at 0, 3 and 24 h (p<0.01 in each case), but not at 48 h Papaziogas et al 2001

The time to first request for analgesics was significantly longer in the IV ketamine + ropivacaine infiltration group compared with the placebo group (p<0.05) Papaziogas et al 2001

Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with significantly lower VAS pain scores at 0, 0.5, 1, 2, 3 and 4 h after arrival in PACU, then at discharge and at 10 h (p<0.05 in each case) but not at 24 or 48 h; and also reduced VRS pain scores at all time points, except at 24 h (p<0.05) Michaloliakou et al 1996

Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with a significantly greater proportion of patients without pain on arrival in PACU and with only mild pain at discharge (p<0.001 in each case) Michaloliakou et al 1996

Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with a significantly longer time to first analgesic request (p<0.001) Michaloliakou et al 1996

Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with a significantly shorter time to discharge from PACU (p<0.05), although the time to the first bowel movement was similar in both groups Michaloliakou et al 1996

Compared with placebo, a regimen of strong opioid plus conventional NSAID, followed by LA wound infiltration, was associated with a significantly reduced nausea scores in PACU (p<0.05), but there was no significant difference at any other time Michaloliakou et al 1996

PROSPECT Recommendations

Clinical Practice

Clinical experience with the paravertebral nerve block is not widespread. This technique is considered to be more complex, and thus it may be associated with a higher incidence of complications than other local anaesthetic techniques (IP/infiltration)

Laparoscopic Cholecystectomy-specific evidence

General anaesthesia + paravertebral blockade significantly reduced VAS pain scores at rest and during activity compared with general anaesthesia alone at 6, 12, 24, 36 and 48 h (p<0.05 in each case), but not at 72 h; abdominal and shoulder VAS pain scores were significantly lower at 6 h only (p<0.05 in each case)&nbsp Naja et al 2004

General anaesthesia + paravertebral blockade significantly increased the proportion of patients who had VAS scores of less than 3 on movement, coughing and walking, up to 48 h postoperatively (p<0.05 in each case) Naja et al 2004

General anaesthesia + paravertebral blockade significantly reduced analgesic use compared with general anaesthesia alone at 0–36 h (p<0.05 in each case) (1 mg/kg IM pethidine was given in the first 12 hours if VAS 4 or greater; next 12 hours: 2 tablets oral dextropropoxyphene, every 6 hours, if VAS 4 or greater) Naja et al 2004

The incidence of nausea, but not vomiting, was significantly reduced in the general anaesthesia + paravertebral blockade group compared with the general anaesthesia alone group at 6 and 12 h (p<0.05 in each case) Naja et al 2004

General anaesthesia/bilateral paravertebral blockade was not significantly different from general anaesthesia alone for the time taken to defecation or to passing bowel gas, or for the duration of recovery room or hospital ward stay Naja et al 2004

A study that compared pre-operative lumbar spinal LA + strong opioid with placebo showed that the incidence of nausea/vomiting and the duration of hospital stay were similar in both groups Motamed et al 2000

PROSPECT Recommendations

Pre-operative oral carbohydrate is not recommended (Grade A), due to a lack of analgesic efficacy (procedure-specific evidence, LoE 1) and inconsistent effects on the incidence of PONV (procedure-specific evidence, LoE 1)

Clinical Practice

Transferable Evidence from Other Procedures

A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritis, urinary retention or respiratory depression Marret et al 2005

A large randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002

Conventional NSAIDs and COX-2 selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003

Short-term use of conventional NSAIDs or COX-2 selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004

One study measured parameters of pulmonary function and found that the values of FEV1 and FEF25–75 were significantly higher at 4 h after surgery in the ketorolac group compared with the placebo group (p<0.05) Liu et al 1993

One study out of one showed that tenoxicam (20 mg) + ondansetron (4 mg), administered in 20 ml saline before induction of anaesthesia, significantly reduced the time to first flatus compared with ondansetron alone (p<0.05) Elhakim et al 1995

Two studies out of seven that recorded the incidence of nausea and/or vomiting, showed that conventional NSAIDs significantly reduced the incidence of nausea and/or vomiting compared with placebo or no treatment Elhakim et al 1995Click here for more information

One study out of one found no significant difference for the duration of hospital stay between IM ketorolac, administered intra-operatively pre- and post-procedure, and placebo Lane et al 1996

One study out of one found no significant difference for the time to hospital discharge between IM diclofenac, administered after induction of anaesthesia (n=26), and placebo (n=23) Wilson et al 1994

One study which compared IM ketorolac with IM diclofenac, administered 30 min prior to end of surgery, showed that there was no significant difference in VAS pain scores, opioid use and incidence of nausea or vomiting between groups Fredman et al 1995

PROSPECT Recommendations

Intra-operative COX-2-selective inhibitors are recommended at the end of surgery to ensure analgesia when the patient wakes up (Grade D, LoE 4)

COX-2-selective inhibitors may be more appropriate than conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (transferable evidence, LoE 1)

It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4)

Clinical Practice

Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004

Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a

Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

Intra-operative dextromethorphan is not recommended (Grade D) because procedure-specific evidence for analgesic efficacy is limited and transferable evidence is inconclusive (LoE 4)

Intra-operative ketamine by infusion is not recommended (Grade D) because procedure-specific evidence is limited, despite some analgesic efficacy in other procedures (transferable evidence, LoE 1)

Intra-operative magnesium by infusion is not recommended (Grade B), because there is evidence for a lack of analgesic efficacy (procedure-specific evidence, LoE 1)

Clinical Practice

NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its CNS adverse effects, toxicity and for causing dysphoria

Transferable Evidence from Other Procedures

Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genito-urinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine Bell et al 2006

Administration of intraoperative magnesium sulphate as an adjuvant analgesic in patients undergoing open cholecystectomy resulted in better pain relief and comfort in the first postoperative hour compared with placebo (sleep quality during first postoperative night was better in the magnesium group compared to placebo p< 0.05), but it did not significantly decrease the postoperative morphine requirement (total n=50) Bhatia et al 2004

A study in gynaecological surgery that compared magnesium with placebo (placebo group received saline, magnesium groups received 40 mg/kg at induction, followed by either, saline, or magnesium infusion 10 mg/kg or 20 mg/kg), showed that morphine consumption was higher in the placebo group compared with the magnesium groups (n=80) Seyhan et al 2006

A quantitative systematic review found that dextromethorphan does not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases Duedahl et al 2006

In abdominal hysterectomy, NMDA-receptor antagonists provided no significant benefit over placebo for reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the specific type of agent and timing of administration Burstal et al 2001Click here for more information

Laparoscopic Cholecystectomy-specific evidence

IV ketamine infusion significantly reduced pain compared with placebo: VAS pain scores at rest at 2–4 h (p<0.05 in each case) but not at 0, 1, 8 or 20 h; VRS pain scores at 2 and 3 h (p<0.05 in each case), but not at other time points Ayoglu et al 2005

IV ketamine infusion significantly reduced cumulative opioid use compared with placebo at 2 and 3 h (p<0.05 in both cases), but not at other time points Ayoglu et al 2005

IV ketamine infusion significantly reduced VAS pain scores at rest compared with magnesium at 4 and 20 h (p<0.05 in both cases), but not at 0–4 or at 8 h; ketamine also significantly reduced VRS pain scores compared with magnesium at 4 h (p<0.05), but not at other time points Ayoglu et al 2005

Total pethidine consumption (1 mg/kg IM pethidine was given if requested) was significantly higher in the intra-operative IM dextromethorphan group compared with the pre-operative IM dextromethorphan group (p<0.0001) Wu et al 1999

Laparoscopic Cholecystectomy-specific evidence

IM pethidine significantly reduced opioid use in the recovery room (0.25 mg/kg IV pethidine was given every 10 minutes, as needed, up to 4 doses in the first hour postoperatively) compared with placebo (p<0.05) Lane et al 1996

There were no significant differences between IV morphine and placebo for VAS pain scores at rest or on coughing at any time point (0–180 min) and both groups took a similar length of time to first analgesic request Munoz et al 2002

There were no significant differences in VAS pain scores between IM pethidine and placebo groups over the first 24 h following surgery Lane et al 1996

There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for VAS pain scores at rest or on coughing at any time point (0–180 min) Munoz et al 2002

There was no significant difference between the IV morphine and placebo groups for the incidence of postoperative emesis Munoz et al 2002

There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for opioid use or the incidence of emesis. All IV morphine groups took similar length of time for first analgesia request Munoz et al 2002

IM pethidine and placebo groups took a similar length of time to first analgesic request Lane et al 1996

There was no significant difference between the IM pethidine and placebo groups for the duration of hospital stay Lane et al 1996

PROSPECT Recommendations

There is no evidence that intra-operative administration is of greater analgesic benefit than pre- or postoperative administration

Clinical Practice

Long-acting local anaesthetics are preferred to short-acting local anaesthetics for analgesia by local injection

Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile

The dose of LA must be monitored to ensure that maximum dose limits are not exceeded, especially if both infiltration and IP LA techniques are used

Transferable Evidence from Other Procedures

A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block showed that port-site infiltration did not reduce postoperative pain after laparoscopy, while intraperitoneal infiltration was associated with a statistically significant but clinically questionable effect on postoperative pain, and mesosalpinx local anaesthetic block reduced postoperative pain to some extent after laparoscopy Møiniche et al 2000

A qualitative systematic review of incisional local anaesthesia for postoperative pain relief after abdominal operations showed that except for herniotomy, there was a lack of evidence for a beneficial effect of incisional local anaesthesia on postoperative pain Møiniche et al 1998

Two quantitative systematic reviews of studies performed in a variety of procedures found no significant benefit of preincisional LA wound infiltration compared with similar postincisional wound infiltration for reducing pain scores Møiniche et al 2002

Laparoscopic Cholecystectomy-specific evidence

Nine out of 11 studies showed a significant benefit of LA wound infiltration over placebo or no treatment for reducing VAS pain scores, see Table 2a for details Click here for more information

In one study out of one, the proportion of patients with most severe pain located to the right lower abdominal wall on day 2 was significantly lower in the LA (bupivacaine) infiltration group compared with the placebo group (p=0.012) Ure et al 1993

In one study out of one, the proportion of patients with no pain after 5 h was significantly higher in the LA wound infiltration group compared with the placebo group (p=0.03) Ure et al 1993

Two studies out of two found that LA wound infiltration significantly increased the time to first analgesic demand compared with placebo (p<0.05 in both cases) Papaziogas et al 2001

Six studies out of 11 reported that LA wound infiltration reduced analgesic consumption compared with placebo or no treatment, see Table 2a for details; each of those studies also showed significantly reduced VAS pain scores with LA wound infiltration Click here for more information

In one study out of one, the rate of same-day discharge was significantly higher in the LA wound infiltration (bupivacaine + epinephrine) group compared with the placebo group (p<0.05) Dath and Park 1999

There were no significant differences between IP LA and intrawound LA for VAS pain scores at 1, 2, 4 or 8 h postoperatively, or at discharge, or for total analgesic use (postoperative analgesia was IM Cyclimorph or 2 x co-proxamol tablets, as required) Johnson et al 1999

There were no significant differences between LA wound infiltration and placebo groups for the duration of hospital stay in two out of two studies Lepner et al 2003

There were no significant differences for VAS pain scores between pre-incisional and postoperative LA administration groups at any of the time points recorded (i.e. 1, 3, 5, 7 and 12 h in the Sarac et al 1996

Clinical Practice

Long-acting local anaesthetics are preferred to short-acting local anaesthetics for analgesia by local injection

Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile

The dose of LA must be monitored to ensure that maximum dose limits are not exceeded, especially if both infiltration and IP LA techniques are used

Transferable Evidence from Other Procedures

A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block showed that port-site infiltration did not reduce postoperative pain after laparoscopy, while intraperitoneal infiltration was associated with a statistically significant but clinically questionable effect on postoperative pain, and mesosalpinx local anaesthetic block reduced postoperative pain to some extent after laparoscopy Møiniche et al 2000

A qualitative systematic review of incisional local anaesthesia for postoperative pain relief after abdominal operations showed that except for herniotomy, there was a lack of evidence for a beneficial effect of incisional local anaesthesia on postoperative pain Møiniche et al 1998

IP instillation at the start of surgery is more favourable than administration at the end of surgery (procedure-specific evidence, LoE 1), although this is from limited evidence and requires confirmation from further studies before a recommendation can be made

Clinical Practice

Long-acting local anaesthetics are preferred to short-acting local anaesthetics

The dose of LA must be monitored to ensure that maximum dose limits are not exceeded, especially if both infiltration and IP LA techniques are used

Transferable Evidence from Other Procedures

A qualitative and quantitative systematic review of intraperitoneal, port-site infiltration and mesosalpinx block showed that intraperitoneal infiltration was associated with a statistically significant but clinically questionable reduction of postoperative pain, and mesosalpinx local anaesthetic block, but not port-site infiltration, reduced postoperative pain to some extent after laparoscopy Møiniche et al 2000

Laparoscopic Cholecystectomy-specific evidence

Fourteen studies out of 23 showed a significant benefit of intraperitoneal LA over placebo or no treatment for reducing VAS pain scores, see Table 3 for details; in two out of nine studies that did not find significant differences between groups, the comparator was IV strong opioid Click here for more information

Four studies out of six showed a significant benefit of intraperitoneal LA over placebo for reducing VRS pain scores, see Table 3 for details

In one study, the same day discharge rate was significantly higher in all groups receiving intraperitoneal LA (15 ml 0.5% bupivacaine) compared with the placebo group (p<0.02) Paulson et al 2003

Three systematic reviews of local anaesthesia in laparoscopic cholecystectomy have found some evidence that intraperitoneal LA reduces pain after surgery, although the overall quality of the studies was not high and there were some conflicting results Bisgaard 2006

Administration of IP bupivacaine at the start of surgery significantly reduced VAS pain scores compared with IP bupivacaine administration at the end of surgery at 8, 12 and 24 h following surgery (p<0.05 in each case), but not at 0 or 4 h, and VRS pain scores at 4, 8 and 24 h (p<0.05 in each case), but not at 0 or 12 h Pasqualucci et al 1996

Administration of IP bupivacaine at the start and end of surgery was significantly superior to administration at the end of surgery alone for reducing VAS pain scores at 0, 4, 8 and 24 h following surgery (p<0.05 in each case) but not at 12 h in one study Pasqualucci et al 1994

Administration of IP bupivacaine at the start and end of surgery sugnificantly reduced VRS pain scores at 0, 4, 8 and 12 h compared with administration at the end of surgery alone (in all cases, p<0.05) but not at 24 h postoperatively in one study Pasqualucci et al 1994

Administration of IP bupivacaine at the start and end of surgery was significantly superior to administration at the start of surgery alone for reducing VAS pain scores at 0 and 4 h (in both cases, p<0.05) Pasqualucci et al 1996

Administration of IP bupivacaine at the start and end of surgery was significantly superior to administration at the start of surgery alone for reducing VRS pain scores at 0 h (p<0.05) Pasqualucci et al 1996

Administration of IP bupivacaine at the start of surgery significantly reduced analgesic use (30 mg IV ketorolac was given, as necessary) compared with IP bupivacaine administration at the end of surgery (p<0.05) Pasqualucci et al 1996

Administration of IP bupivacaine at the start and end of surgery significantly reduced analgesic (30 mg IV ketorolac was given, as necessary) requirement compared with administration at the end of surgery alone (p<0.05) Pasqualucci et al 1994

The incidence of nausea and vomiting was lower in the start of surgery IP LA administration group compared with the end of surgery IP LA administration group, although p values were not given Pasqualucci et al 1996

Administration of IP bupivacaine at the start and end of surgery reduced the incidence of nausea and vomiting compared with administration at the end of surgery alone Pasqualucci et al 1994

Incisional and intra-abdominal VAS pain scores at rest and during coughing were significantly reduced in the IP LA + IV strong opioid group compared with the placebo group at 1 and 2 h following surgery (p<0.05, in all cases), but not at other time points (4, 6, 12 or 24 h postoperatively); shoulder-tip pain VAS scores and VRS pain relief scores were also similar Hernandez-Palazon et al 2001

Abdominal and shoulder VAS pain scores were significantly lower in the IP LA + saline lavage and suction group compared with the placebo group (p<0.05) Tsimoyiannis et al 1998

Adding ketamine or magnesium to IP bupivacaine resulted in a significant reduction in VAS shoulder pain scores compared with both IP LA alone and placebo (p<0.05 in each case) Abdel-Raouf + Amer 2004

One out of two studies showed that IP LA + IP NSAID and IP LA + IV NSAID treatment increased the time to first analgesic request compared with placebo, although p values were not presented Elhakim et al 2000a

Adding ketamine or magnesium to IP bupivacaine resulted in a significantly longer time to first analgesic request compared with both IP LA alone and placebo (p<0.05 in each case) Abdel-Raouf + Amer 2004

The number of patients needing rescue analgesics was significantly lower in the IP LA + IV NSAID group, but not the IP LA + IP NSAID group, compared with the placebo group Jabbour-Khoury et al 2005

The proportion of patients requiring no analgesia was significantly lower in the IP LA group compared with the saline lavage + suction group (p<0.05) Tsimoyiannis et al 1998

In one of two studies, the incidence of vomiting was significantly lower in the IP LA + IV NSAID group, but not the IP LA + IP NSAID group, compared with the placebo group (p<0.05) Jabbour-Khoury et al 2005

The incidence of nausea and vomiting was significantly lower in the IP LA + saline lavage and suction group compared with the placebo group (p<0.05, in both cases) Tsimoyiannis et al 1998

The incidence of nausea and vomiting and the duration of hospital stay were not significantly different between the IP LA group and the saline lavage and suction group Tsimoyiannis et al 1998

In one study, patients receiving IP tenoxicam (20 mg) and 200 ml lidocaine (0.1%) + 2 ml IV saline, administered at the end of surgery, took significantly less time to bowel recovery compared with the placebo group (p<0.05) Elhakim et al 2000a

There were no significant differences between IP LA and intrawound LA for VAS pain scores at 1, 2, 4 or 8 h postoperatively, or at discharge, or for total analgesic use (postoperative analgesia was IM Cyclimorph or 2 x co-proxamol tablets, as required) Johnson et al 1999

In one study that compared IP bupivacaine or bupivacaine + epinephrine with placebo or no treatment, the proportion of patients with strong or unbearable pain was found to be similar in the three groups Scheinin et al 1995

Two out of three studies found that IP LA treatment did not increase the time to first analgesic request compared with placebo; see Table 3

There were no significant differences between the IP LA + IP strong opioid group compared with the placebo group at any time (i.e. at 1, 2, 4, 6, 12 or 24 h postoperatively) for incisional, intra-abdominal or shoulder VAS pain scores, at rest or during coughing, or for VRS pain relief scores Hernandez-Palazon et al 2003

There were no significant differences between IP ropivacaine doses groups [20 ml (300 mg) 0.75% and 20 ml (100 mg) 0.25%], administered once at the start of surgery and once at the end of surgery, for visceral or parietal VAS pain scores at rest, during coughing or during mobilisation Labaille et al 2002

One study showed that the addition of epinephrine to IP LA solution did not confer any benefit for reducing pain scores: VRS pain score at rest or on movement; the incidence of shoulder pain and the proportion of patients with strong or unbearable pain Scheinin et al 1995

One study that compared two different doses of ropivacaine, 20 ml (300 mg) 0.75% ropivacaine with 20 ml (100 mg) 0.25% ropivacaine, administerd once at the start and once at the end of surgery, showed that both dose groups consumed similar amounts of opioids (see Table 2.1 for details) Labaille et al 2002

One study that compared bupivacaine (0.125%) with bupivacaine (0.25%), both regimens administered at the end of surgery, showed no significant difference for VAS pain scores at rest, on deep inspiration or on coughing Raetzel et al 1995

One study that compared bupivacaine (0.125%) with bupivacaine (0.25%), both regimens administered at the end of surgery, showed that both dose groups consumed similar amounts of opioids Raetzel et al 1995

One study compared 0.25% IP bupivacaine + 2 mg IP or IV morphine, administered at the end of surgery, with placebo showed that there was no significant difference between the groups for incidence of nausea/vomiting Hernandez-Palazon et al 2003

One study that compared bupivacaine (0.125%) with bupivacaine (0.25%), both regimens administered at the end of surgery, showed no significant difference between both dose groups for incidence of nausea and vomiting Raetzel et al 1995

A study that compared 125% IP bupivacaine with 0.25% IP bupivacaine, both regimens adminstered at the end of surgery showed that FVC was significantly more impaired in the group receiving the higher dose of bupivacaine (0.25%) compared with the lower dose (0.125%) Raetzel et al 1995

PROSPECT Recommendations

IP opioids are not recommended due to limited evidence for analgesic benefit (Grade D)

Clinical Practice

Since pethidine has an additional local anaesthetic action, which morphine does not, it can be expected to be more efficacious than morphine when given intraperitoneally

Transferable Evidence from Other Procedures

One study found that the combination of intraperitoneal bupivacaine and intraperitoneal pethidine was better than the combination of IP bupivacaine and IM pethidine for postoperative analgesia in patients undergoing laparoscopic tubal ligation; pain scores were significantly lower in the group receiving IP pethidine both at rest (p<0.01) and with movement (p<0.05) (n=100) Colbert et al 2000

A study that compared IP strong opioid (pethidine) with IM/IV strong opioid (pethidine) on a background of IP LA showed that total PCA opioid consumption during the first 24 h after surgery was significantly lower in the IP pethidine group compared with the IM pethidine group (p<0.001) O'Hanlon et al 2002

A study that compared IP morphine with IM/IV morphine on a background of IP LA, found that incisional and intra-abdominal VAS pain scores were significantly lower in the IV morphine group compared with the IP morphine group at 1 and 2 h following surgery (in both cases, p<0.05), but not at 4, 6, 12 or 24 h Hernandez-Palazon et al 2003

A study that compared IP strong opioid (morphine) with IM/IV strong opioid (morphine) on a background of IP LA, showed that postoperative PCA metamizol use was significantly lower in the IV morphine group compared with the IP morphine group in the first 24 h following surgery (p<0.05) Hernandez-Palazon et al 2003

Clinical Practice

Combined epidural/general anaesthesia (CEGA) may be utilised in certain patients at high risk of pulmonary complications, although the surgical procedure does not justify the use of this anaesthetic technique in most patients where the risk of side-effects associated with the epidural technique may outweigh the potential benefits.

Prophylactic anti-emetics, such as ondansetron or dexamethasone, may be administered intravenously before emergence from anaesthesia

Total intravenous anaesthesia (TIVA) or balanced anaesthesia with inhalational agents (avoid halothane), short-acting opioids (fentanyl, alfentanil, remifentanil), and muscle relaxants may be used

TIVA offers an alternative to inhalational anaesthesia, and whilst rapid recovery from anaesthesia and reduction in nausea and vomiting are recognised benefits, the analgesic components of TIVA have a very short duration and do not contribute to improved postoperative analgesia

Transferable Evidence from Other Procedures

[None cited]

Laparoscopic Cholecystectomy-specific evidence

Combined epidural/general anaesthesia was significantly superior to total intravenous anaesthesia for reducing VAS pain scores at 2, 3 and 4 h (p<0.05 in each case), but not at 0–1 h; the incidence of abdominal and shoulder pain was similar in both groups Luchetti et al 1996

The recovery score (Steward test) was significantly superior in the combined epidural/general anaesthesia group compared with the total intravenous anaesthesia group at 4 and 6 minutes (p<0.05, in both cases), but not at other times Luchetti et al 1996

IV butorphanol was associated with a significantly lower proportion of patients with moderate-severe pain on the VRS scale compared with IV fentanyl (p<0.05; both administered 2 minutes before induction of anaesthesia)&nbsp Usmani et al 2004

The time to first rescue analgesic (1.5 mg/kg IV tramadol hydrochloride was given to patients complaining of moderate to severe pain) was significantly longer in the butorphanol group compared with the fentanyl group (p<0.05)&nbsp Usmani et al 2004

A study that compared three different doses (0.6%, 1.2% and 1.8%) of isoflurane-fentanyl combination with isoflurane alone for maintenance anaesthesia, showed that the time to tracheal extubation and to eye opening was significantly reduced in the 0.6% end-tidal isoflurane-fentanyl group compared with the isoflurane alone group (p<0.01), although the times to spontaneous breathing and to discharge to the ward were similar in all groups Munoz et al 2005

The time to tracheal extubation and to eye opening was significantly reduced in the 0.6% end-tidal isoflurane-fentanyl group compared with the other two groups (1.2% and 1.8%) (p<0.001), although the times to spontaneous breathing and to discharge to the ward were similar in all three groups Munoz et al 2005

The time to tracheal extubation and to eye opening was significantly reduced in the 1.2% end-tidal isoflurane-fentanyl group compared with the 1.8% group (p<0.05)&nbsp Munoz et al 2005

The incidence of nausea, but not vomiting, was significantly reduced in the remifentanil + propofol group compared with the remifentanil + desflurane group (p<0.05) Grundmann et al 2001

In a study that compared combined epidural/general anaesthesia with total intravenous anaesthesia, there were no significant differences between groups for the incidence of nausea or vomiting Luchetti et al 1996

IV butorphanol and IV fentanyl administered 2 minutes before induction of ananesthesia were associated with similar incidence of nausea and vomiting, time to orientation and discharge, and the incidence of excessive drowsiness were similar in both groups Usmani et al 2004

There were no significant differences between different doses (0.6%, 1.2% and 1.8%) of isoflurane-fentanyl combination and isoflurane alone for VAS pain scores at rest or on coughing at any of the time points recorded (i.e. at 0, 15, 30, 45, 60, 90 or 120 minutes postoperatively) Munoz et al 2005

There were no significant differences between the remifentanil + propofol and remifentanil + desflurane groups for reducing VAS pain scores (both groups had lower pain scores at 30–90 minutes after arrival in PACU than at arrival in PACU) Grundmann et al 2001

The proportion of patients requiring opioid and the amount of opioid used were similar between different doses of isoflurane-fentanyl combination (0.6%, 1.2% and 1.8%) and isoflurane alone Munoz et al 2005

There were no significant differences between three different doses (0.6%, 1.2% and 1.8%) of isoflurane-fentanyl combination and isoflurane alone for Apfels' risk score for PONV and the incidence of nausea and vomiting was also similar in both groups Munoz et al 2005

PROSPECT Recommendations

Clinical Practice

The gasless technique requires additional equipment (currently no proven cost:benefit ratio), operating time may be increased and surgical view of the cholecystectomy may be compromised

Transferable Evidence from Other Procedures

One study found that there were no clinically important differences in cardiovascular and systemic responses between patients undergoing CO2 or gasless laparoscopy for colonic disease (n=17) Schulze et al 1999

Laparoscopic Cholecystectomy-specific evidence

In one out of the two studies, the incidence of shoulder pain was significantly lower (p<0.05) in the gasless or minimal CO2 insufflation pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group Lindgren et al 1995Click here for more information

In one study out of one, the number of patients with no pain in the recovery room was significantly higher in the gasless CO2 insufflation pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group Uen et al 2002

In one out of one study, the duration of drowsiness was significantly lower (p<0.001) in the minimal CO2 insufflation pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group&nbsp Lindgren et al 1995

In three out of the three studies, there were no significant differences between gasless or minimal CO2 insufflation pneumoperitoneum and conventional CO2 pneumoperitoneum groups for VAS pain scores (see Table 4 for details)

There were no significant differences between gasless laparoscopic cholecystectomy and low-pressure laparoscopic cholecystectomy for VAS pain scores at any time point (VAS pain scores recorded at 4, 8, 12 and 24 h postoperatively and then each morning, for 1 week) Vezakis et al 1999

The incidence of shoulder pain was significantly greater in the gasless laparoscopic cholecystectomy group compared with the low-pressure laparoscopic cholecystectomy group (p<0.05) Vezakis et al 1999

In three out of three studies, analgesic use was similar in both gasless or minimal CO2 insufflation pneumoperitoneum and conventional CO2 pneumoperitoneum groups (see Table 4 for details); in one study out of one the length of time to complete pain relief was also similar in both groups Larsen et al 2001

Analgesic use was similar in both gasless pneumoperitoneum and low-pressure pneumoperitoneum group Vezakis et al 1999

One out of the three studies reported that PONV requiring droperidol was significantly reduced in the minimal CO2 insufflation pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group (p<0.05) Lindgren et al 1995

There was no significant difference between gasless pneumoperitoneum and low-pressure pneumoperitoneum groups for the incidence of nausea or vomiting Vezakis et al 1999

In two studies out of two, there were no significant differences between the gasless pneumoperitoneum and conventional carbon dioxide (CO2) pneumoperitoneum groups for the duration of hospital stay Larsen et al 2001Click here for more information

The duration of hospital stay was similar in gasless pneumoperitoneum and low-pressure pneumoperitoneum groups Vezakis et al 1999

The incidence of shoulder pain was significantly lower in the low-pressure laparoscopic cholecystecomy group compared with the gasless laparoscopic cholecystectomy group (p<0.05)&nbsp Vezakis et al 1999

In two studies out of four, analgesic use was significantly reduced in the low pressure CO2 pneumoperitoneum group compared with the conventional CO2 pneumoperitoneum group, see Table 5 for details Barczynski and Herman 2003

In one study out of one, low pressure CO2 pneumoperitoneum was significantly superior to conventional CO2 pneumoperitoneum in terms of pulmonary function and duration of hospital stay Wallace et al 1997

There were no significant differences between gasless laparoscopic cholecystectomy and low-pressure laparoscopic cholecystectomy for VAS pain scores at any time point (VAS pain scores recorded at 4, 8, 12 and 24 h postoperatively and then each morning, for 1 week) Vezakis et al 1999

Analgesic use was similar in both gasless pneumoperitoneum and low-pressure pneumoperitoneum group Vezakis et al 1999

Laparoscopic Cholecystectomy-specific evidence

PROSPECT Recommendations

A smaller total size of trocar incision is not recommended to reduce postoperative pain (Grade D, LoE 4) because of inconsistent procedure-specific evidence for analgesic benefit

Clinical Practice

[None cited]

Transferable evidence from Other Procedures

[None cited]

Laparoscopic Cholecystectomy-specific evidence

Seven out of 12 studies found that a smaller total size of trocar incision significantly reduced VAS pain scores compared with conventional total size of trocar incision (25 mm or greater), see Table 7 for details

Five out of 13 studies found that a smaller total size of trocar incision significantly reduced analgesic use compared with conventional total size of trocar incision (25 mm or greater), see Table 7 for details; of those five studies, three also showed significantly lower VAS pain scores with smaller total size of trocar incision Bresadola et al 1999Click here for more information

Two studies out of three found no significant differences between the smaller total size and conventional (25 mm or greater) total size of trocar incision groups for the incidence of nausea and vomiting Ainslie et al 2003

In four out of four studies, pulmonary function values were similar in both the smaller total size and conventional (25 mm or greater) total size of trocar incision groups Ainslie et al 2003

There were no significant differences between the smaller total size of trocar incision and the conventional (25 mm or greater) total size of trocar incision groups for the duration of hospital stay in eight studies out of eight; see Table 7 for details Click here for more information

In one study out of one, the time taken to resume stool passage was similar in both the smaller total size of trocar incision and conventional (25 mm or greater) total size of trocar incision groups Sarli et al 2003

PROSPECT Recommendations

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

A randomised prospective study of radially expanding trocars showed that radially expanding trocars are safe and effective, and less likely than conventional trocars to result in intra-operative or postoperative complications Bhoyrul et al 2000Click here for more information

Laparoscopic Cholecystectomy-specific evidence

Epigastric wound VAS pain scores were significantly lower in the radially expanding trocar group compared with the conventional trocar group from day 1 to day 3 following surgery (p<0.05, in all cases); subumbilical VAS pain scores over the same period were similar Lam et al 2000

PROSPECT Recommendations

No recommendation for surgeon’s position can be made because of limited procedure-specific evidence (LoE 1)

Clinical Practice

The ‘French’ technique is associated with a better display of the anatomy of Calot’s triangle

The ‘American’ technique has a lower trajectory for instrument contact with the bowel and may increase the rate of perforation of the bowel

Transferable Evidence from Other Procedures

[None cited]

Laparoscopic Cholecystectomy-specific evidence

VRS pain scores were significantly lower in the 'French' technique group compared with the 'American' technique group at 48 h following surgery (lying VAS p=0.034; sitting VAS p=0.021), but not at 6 or 24 h Kum et al 1996

One study that compared the 'French' and 'American' technique showed that FEV1 was significantly greater in the 'French' technique group compared with the 'American' technique group at 6, 24 and 48 h postoperatively (p=0.001 in all cases) Kum et al 1996

There were no significant differences between the 'French' and 'American' techniques for opioid or NSAID consumption (postoperative analgesia was IV tramadol or enteral ibuprofen, on request; doses not specified) Kum et al 1996

PROSPECT Recommendations

No recommendation can be made for one form of dissection over another on the basis of impact on pain

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

[None cited]

Laparoscopic Cholecystectomy-specific evidence

In one study out of two, postoperative VAS pain scores were significantly lower in the ultrasonic shears group compared with the electrocautery group at 4 and 24 h (p=0.002; p=0.003, respectively), but not at 1 and 2 h Cengiz et al 2005

One out of two studies found that postoperative nausea scores (VAS) were significantly reduced in the ultrasonic shears group compared with the electrocautery group at 2, 4 and 24 h (p=0.023; p=0.002; p<0.001, respectively), but not at 1 h Cengiz et al 2005

PROSPECT Recommendations

Use of saline lavage, followed by suction of the saline, is recommended (Grade A) based on evidence for a reduction in postoperative abdominal and shoulder pain, as well as a reduction in supplementary analgesic use (procedure-specific evidence, LoE 1)

Use of a subhepatic drain is not recommended (Grade D) because of inconsistent evidence for an analgesic benefit (LoE 4)

Aspiration of the pneumoperitoneum gas is not recommended (Grade D) because of limited procedure-specific evidence (LoE 1)

A study that compared saline peritoneal lavage with no lavage during laparoscopic surgery observed that less pain was found in the group undergoing saline peritoneal lavage at 4 and 24 h (total n=173) O'Boyle et al 2002

Laparoscopic Cholecystectomy-specific evidence

PCA opioid demands (1 mg/ml bolus doses of morphine were given, to a maximum of 6 mg/h) were significantly lower in the active aspiration group compared with the control group (p<0.05); but there was no significant difference between groups for total morphine use Fredman 1994

Abdominal and shoulder VAS pain scores were significantly lower in the saline lavage group compared with the control group at 2–48 h (p<0.05, in all cases), but not at 72 h Tsimoyiannis et al 1998

The proportion of patients not requiring analgesia was significantly greater in the saline lavage group compared with the control group (p<0.05) Tsimoyiannis et al 1998

The number of suppositories required (400 mg 4-acetylamino-phenol with 20 mg codeine phosphate + 50 mg caffeine was given rectally, as required), and the proportion of patients requiring parenteral pethidine (one 50 mg dose was given if the suppositories failed) were significantly lower in the saline lavage group compared with the control group (p<0.05, in both cases) Tsimoyiannis et al 1998

The incidence of vomiting was similar in both groups but the incidence of nausea was significantly lower in the saline lavage group compared with the control group in one study (p<0.05) Tsimoyiannis et al 1998

The proportion of patients not requiring analgesia was significantly higher in the saline lavage + suction group compared with the control group (with or without subhepatic drain in both groups) (p<0.05, in both cases) Tsimoyiannis et al 1998Click here for more information

The incidence of nausea, vomiting and blood loss and the duration of hospital stay were similar in both saline + suction and control groups (with or without subhepatic drain in both groups), although quantitative analysis shows a benefit of saline + suction for reducing PONV&nbsp Tsimoyiannis et al 1998Click here for more information

VAS pain scores appear to be not significantly different between saline lavage + suction and saline lavage with no suction, at 2, 6, 12, 24, 48 or 72 h, though statistics are not clear Tsimoyiannis et al 1998

The incidence of nausea and vomiting and the duration of hospital stay were similar in both saline lavage + suction and saline lavage with no suction groups Tsimoyiannis et al 1998

Three studies out of five found no significant differences for VAS pain scores for drainage compared with control, see Table 8b for details; in addition, the number of patients with abdominal and shoulder pain, as well as the duration of postoperative and shoulder pain were similar in both groups in one study out of one Hawasli and Brown 1994Click here for more information

Analgesia use (see Table 8b for details) was similar in both groups in three out of three studies Nursal et al 2003

PROSPECT Recommendations

No recommendation regarding intra-operative fluid management can be made because of limited procedure-specific evidence (LoE 1)

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

[None cited]

Laparoscopic Cholecystectomy-specific evidence

There were no significant differences between the restrictive fluid administration and liberal fluid administration groups for reducing VAS pain scores in the early (i.e 0–4 h after surgery) or late (from the evening on the day of surgery to the evening on the third postoperative day) postoperative periods Holte et al 2004

FVC and FEV1 were significantly reduced in the restrictive fluid administration group compared with the liberal fluid administration group at 2 h postoperatively for FVC, and 2 and 4 h postoperatively for FEV1 (p<0.05, in all cases); PEF was similar in both groups Holte et al 2004

Clinical Practice

Transferable Evidence from Other Procedures

A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritis, urinary retention or respiratory depression Marret et al 2005

A large randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002

Conventional NSAIDs and COX-2 selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003

Short-term use of conventional NSAIDs or COX-2 selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004

One study measured parameters of pulmonary function and found that the values of FEV1 and FEF25–75 were significantly higher at 4 h after surgery in the ketorolac group compared with the placebo group (p<0.05) Liu et al 1993

One study out of one showed that tenoxicam (20 mg) + ondansetron (4 mg), administered in 20 ml saline before induction of anaesthesia, significantly reduced the time to first flatus compared with ondansetron alone (p<0.05) Elhakim et al 1995

One study showed that the number of patients needing rescue analgesics (type, dose and time of administration not stated) was significantly lower in the IV NSAID + IP LA group, but not the IP NSAID + IP LA group, compared with the placebo group (p<0.05) Jabbour-Khoury et al 2005

The incidence of vomiting was significantly lower in the IV NSAID + IP LA group, but not the IP NSAID + IP LA group, compared with the placebo group (p<0.05) Jabbour-Khoury et al 2005

Two studies out of seven that recorded the incidence of nausea and/or vomiting showed that conventional NSAIDs significantly reduced the incidence of nausea and/or vomiting compared with placebo or no treatment Elhakim et al 1995Click here for more information

One study out of one found no significant difference for the duration of hospital stay between IM ketorolac, administered intra-operatively pre- and post-procedure, and placebo Lane et al 1996

One study out of one found no significant difference for the time to hospital discharge between IM diclofenac, administered after induction of anaesthesia (n=26), and control (n=23) Wilson et al 1994

Postoperative ketoprofen significantly increased VAS pain scores compared with pre-operative ketoprofen during the first 12 h following surgery (p<0.05), with the effect being most evident during the first 3 h (p=0.001), although there was no significant difference between the two groups at 24 h Boccara et al 2005

One study showed no significant difference between IV and IP administration of tenoxicam for VAS pain scores (at rest, on movement or on coughing), opioid use (postoperative opioid was 20 mg IM nalbuphine, every 4 h, or on request), incidence of nausea or vomiting and length of hospital stay&nbsp Elhakim et al 2000a

PROSPECT Recommendations

COX-2-selective inhibitors may be more appropriate than conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (transferable evidence, LoE 1)

It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3) or actual or recent gastroduodenal ulcer history (LoE 4)

Clinical Practice

Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004

Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a

Short-term use of COX-2 selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004

Conventional NSAIDs and COX-2 selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003

Parecoxib/valdecoxib was associated with reduced incidence of vomiting at 24 h post-discharge (p<0.05) compared with placebo but overall incidence of PONV throughout the study period was not reduced Gan et al 2004Click here for more information

PROSPECT Recommendations

Postoperative ketamine by bolus or infusion is not recommended (Grade D) because procedure-specific evidence is limited, despite some analgesic efficacy in other procedures (LoE 1)

Postoperative magnesium by infusion is not recommended (Grade B), because there is evidence for a lack of analgesic efficacy (procedure-specific evidence, LoE 1)

Clinical Practice

NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its CNS adverse effects, toxicity and for causing dysphoria

Transferable Evidence from Other Procedures

Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine Bell et al 2006

A study in gynaecological surgery that compared magnesium with placebo (placebo group received saline, magnesium groups received 40 mg/kg at induction, followed by either saline, or magnesium infusion 10 mg/kg or 20 mg/kg), showed that morphine consumption was higher in the placebo group compared with the magnesium groups (total n=80) Seyhan et al 2006

A quantitative systematic review found that dextromethorphan does not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases Duedahl et al 2006

In abdominal hysterectomy, NMDA-receptor antagonists provided no significant benefit over placebo for reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the specific type of agent and timing of administration Burstal et al 2001Click here for more information

Laparoscopic Cholecystectomy-specific evidence

IV ketamine infusion significantly reduced pain compared with placebo: VAS pain scores at rest at 2–4 h (p<0.05 in each case), but not at 0, 1, 8 or 20 h; VRS pain scores at 2 and 3 h (p<0.05 in both cases), but not at other time points Ayoglu et al 2005

IV ketamine infusion significantly reduced VAS pain scores at rest compared with magnesium at 4 and 20 h (p<0.05 in both cases), but not at 0–4 h or at 8 h; ketamine also significantly reduced VRS pain scores compared with magnesium at 4 h (p<0.05), but not at other time points Ayoglu et al 2005

IV ketamine reduced the amount of rescue tramadol used and the number of patients requesting rescue tramadol compared with tramadol (p values not given) (a rescue dose was administered when VAS >5 on the 0–10 scale) Launo et al 2004

IV ketamine and tramadol were equally effective for reducing VAS pain scores 0–24 h after surgery; there were no significant differences between the two treatment groups for VRS pain scores Launo et al 2004

IV magnesium infusion did not significantly reduce VAS or VRS pain scores compared with placebo at any time during 0–20 h Ayoglu et al 2005

Pre-operative and postoperative (R)-ketamine (bolus dose) were similar to placebo for pethidine use in the first 4 h, and for use of paracetamol + codeine at 24 h and 7 days postoperatively (postoperative analgesia: bolus doses of 0.1 mg/kg pethidine, 5-minute lockout, for 4 h, and after discharge, 500 mg paracetamol + 30 mg codeine) Mathisen et al 1999

Clinical Practice

Strong opioids are not associated with a ceiling effect, and thus can provide effective analgesia for most types of surgical procedures

Strong opioids may be used in a variety of preparations and routes of administration, enabling choice for onset, duration of action, and mode of delivery

Most clinical trials showing benefits of intramuscular strong opioids use nurse-administered regimens. In regular clinical practice, full adherence to nurse-administered regimens is not usually achievable, and the full analgesic benefits of intramuscular strong opioids are also not achieved

Intramuscular administration of strong opioids is considered to be more painful than intravenous administration; however, the dose and rapidity of intravenous administration should be assessed to minimise the risk of respiratory depression

Laparoscopic Cholecystectomy-specific evidence

There were no significant differences between IV morphine and placebo for VAS pain scores at rest or on coughing at any time point (i.e. 0–180 minutes) Munoz et al 2002

There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for VAS pain scores at rest or on coughing at any time point Munoz et al 2002

Systemic opioid and placebo groups took a similar length of time to first analgesic request Munoz et al 2002

There was no significant difference between IV morphine and placebo for the incidence of postoperative emesis Munoz et al 2002

There was no significant difference between the IM pethidine and placebo groups for the duration of hospital stay Lane et al 1996

There were no significant differences between groups receiving pre-operative, intra-operative or postoperative IV morphine for opioid use or the incidence of emesis. All IV morphine groups took a similar length of time for first analgesia request Munoz et al 2002

PROSPECT Recommendations

Postoperative weak opioids are not recommended (Grade B) for routine analgesia because of side-effects during recovery (transferable evidence, LoE 1)

Weak opioids are recommended for rescue analgesia (low- to moderate-intensity pain) in addition to the use of other agents (Grade D, LoE 4)

Clinical Practice

Tramadol is a centrally acting analgesic with µ-opioid agonist (M1-metabolite) and aminergic mechanisms of action. For prescription purposes, it is considered a weak opioid or a non-narcotic in most countries

Tramadol is useful in the treatment of postoperative pain of moderate intensity (intravenous and oral administration), providing effective analgesia in the in-patient and ambulatory setting

The opioid-like effects of tramadol on gastrointestinal (transit, secretion) and sphincter function, are of a lesser magnitude than those of strong opioids

At recommended doses, tramadol has no clinically relevant effects on cardiovascular or respiratory parameters, thus the risk of respiratory depression is negligible

Tramadol is beneficial when NSAIDs are contraindicated

The oral solution (drops) of tramadol is useful as rescue medication when paracetamol/NSAID analgesic regimens are used

Opioid adverse effects, especially nausea and dizziness, limit the usefulness of tramadol, but many of the effects are less than for strong opioids

When ondansetron is used for the treatment/prophylaxis of tramadol-induced nausea and vomiting, a decrease in analgesic efficacy has been reported

Transferable Evidence from Other Procedures

Tramadol was more effective than placebo for pain relief in a meta-analysis of post-surgical patients Moore et al 1997

A systematic review found that the combination of dextropropoxyphene 65 mg with paracetamol 650 mg showed similar efficacy to tramadol 100 mg but with a lower incidence of adverse effects Collins et al 2000

A systematic review found that the combination of codeine with paracetamol provided additional pain relief compared with paracetamol alone Moore et al 2000

Laparoscopic Cholecystectomy-specific evidence

Compared with placebo, tramadol significantly reduced VAS pain scores at 30, 45 and 60 minutes postoperatively (in all cases, p=0.01), but not at any other time point in the first 24 h (i.e. at 2, 4, 6, 8, 10, 12, 18 or 24 h Naguib et al 2000

Tramadol treatment was significantly superior to placebo treatment for reducing pain scores recorded by an observer at 30 and 45 minutes following surgery (p=0.01, in both cases)&nbsp Naguib et al 2000

Tramadol significantly reduced supplementary tramadol use only at 30, 45 and 60 minutes postoperatively compared with placebo (p<0.03), but not at any other time point in the first 24 h Naguib et al 2000

One study that compared pre-operative IV tramadol + postoperative IV tramadol PCA with pre-operative IV morphine + postoperative IV morphine PCA, showed that morphine significantly reduced VAS pain scores at 30, 45 and 90 minutes following surgery compared with tramadol (in all cases, p<0.05), but not at any other time (recorded every 2 h until 24 h) or for pain scores recorded by an observer; but not at any other time&nbsp Naguib et al 1998

There were no significant differences between pre-operative IV tramadol + postoperative IV tramadol PCA group and pre-operative IV morphine + postoperative IV morphine group for the time taken to the first analgesic demand or for the proportion of patients not requesting PCA analgesia Naguib et al 1998

The incidence of nausea and vomiting, as well as respiratory rate were similar in both tramadol and placebo groups Naguib et al 2000

A meta-analysis of randomised controlled trials showed that paracetamol combined with PCA morphine induced a significant morphine-sparing effect but did not change the incidence of morphine-related adverse effects in the postoperative period Remy 2005

There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone Altman 2004

Laparoscopic Cholecystectomy-specific evidence

Postoperative administration of propacetamol significantly reduced VAS pain scores between 2 and 5 h postoperatively compared with pre-operative administration (p<0.05); the number of patients with severe pain (VAS 50 mm or greater) was significantly lower in the postoperative administration group compared with the pre-operative administration group (p<0.05) Boccara et al 2005

Ibuprofen sustained-release tablets and paracetamol were associated with similar VRS pain scores all time points (i.e. days 1–7) Owen et al 1997

Pre-operative propacetamol was associated with significantly greater opioid use compared with pre-operative ketoprofen, but there was no significant difference between these agents given postoperatively Boccara et al 2005Click here for more information

The number of patients requiring supplemental nalbuphine, the total dose consumed and the time to first analgesic demand were similar in both pre-operative and postoperative propacetamol groups Boccara et al 2005

The incidence of nausea or vomiting was similar in both pre-operative and postoperative propacetamol groups Boccara et al 2005

There were no significant differences between the paracetamol + codeine and codeine alone groups for VAS pain scores (recorded at 0.5–4 h, then 3 times/day, until 48 h) Chung et al 2004

Supplemental opioid consumption, the time of onset of analgesia and the overall level of pain relief were similar in both paracetamol + codeine and codeine alone groups Chung et al 2004

There were no significant differences between the paracetamol + codeine and codeine alone groups for postoperative nausea; the time to discharge was also similar in both groups Chung et al 2004

PROSPECT Recommendations

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

[None cited]

Laparoscopic Cholecystectomy-specific evidence

One study that compared ropivacaine injected into the bed of the gall bladder and in all portals after surgery and then as intermittent self-administered postoperative PCA versus placebo, showed that ropivacaine significantly decreased VAS pain scores (deep intra-abdominal and coughing pain) compared with placebo, up to 4 hours postoperatively, but not at 8, 12, 16 or 20 h or between 1–7 days following surgery Gupta et al 2002

One study that compared ropivacaine injected into the bed of the gall bladder and in all portals after surgery and then as intermittent self-administered PCA versus placebo showed that opioid consumption 0–20 h postoperatively, and the total amount of analgesics consumed during the first week following surgery were similar in both groups Gupta et al 2002

One study that compared ropivacaine injected into the bed of the gall bladder and in all portals after surgery and then as intermittent self-administered postoperative PCA versus placebo, showed that there were no significant differences between the two groups for the incidence of nausea and vomiting Gupta et al 2002

A study that compared ropivacaine injected into the bed of the gall bladder and in all portals after surgery and then as intermittent self-administered postoperative PCA versus placebo, showed that the time to discharge and also the time to defecate were similar in both groups Gupta et al 2002

A meta-analysis of randomised controlled trials found that compared with systemic opioids, epidural opioids significantly decreased the incidence of atelectasis and had a weak tendency to reduce the incidence of pulmonary infections and pulmonary complications overall, while epidural LAs significantly increased PaO2 and decreased the incidence of pulmonary infections and pulmonary complications overall Ballantyne et al 1998

PROSPECT Recommendations

Postoperative pain is not increased by early discharge (<24 hours) (procedure-specific evidence, LoE 1), which is recommended for other reasons (Grade D)

Clinical Practice

Early discharge is associated with greater patient satisfaction and reduced cost

Transferable evidence from Other Procedures

A study comparing costs and outcomes of inpatient versus outpatient hernia repair, showed that outpatient hernia repair was associated with lower costs and apparent absence of adverse outcomes; although there were no detectable differences between inpatients and outpatients for outcomes such as complication rates, deaths and hernia recurrence, the re-admission rates were higher for inpatients (n=27,036) Mitchell + Harrow 1994

Laparoscopic Cholecystectomy-specific evidence

In one study, VRS pain/discomfort at 1 week and 6 weeks follow-up was similar in the daycare and clinical observation groups Keulemans et al 1998

The outpatient management group consumed significantly more oral analgesic (oxycodone + paracetamol) compared with the inpatient management group prior to PACU discharge (p<0.05), but there were no significant differences between groups for total analgesia used (fentanyl, narcotics, oxycodone + paracetamol; details not given) Curet et al 2002

There were no significant differences in outpatient and inpatient management groups for analgesic consumption (a single dose of 5–10 mg IM morphine was given on request; 500 mg paracetamol + 20 mg codeine was given up to 6 times/day; 500 mg naproxen was also given, up to 3 times/day) during the first 48 h postoperatively Keulemans et al 1998

In two out of two studies, the incidence of PONV (assessed at 4 h and 24 h) Curet et al 2002

In one study out of one, there were no significant differences between inpatient and outpatient management groups for bowel movement Young and O'Connell 2001